title: Orthopedic manifestations and implications for individuals with Costello syndrome.
abstract: Costello syndrome is a rare genetic condition caused by heterozygous alterations in HRAS and characterized by multi-system abnormalities. Individuals with Costello syndrome usually present with severe feeding difficulties in infancy, short stature, coarse facial features, increased tumor risks, cardiac and neurological complications, intellectual disability and orthopedic complications. This study further defines the orthopedic manifestations affecting individuals with Costello syndrome. We studied 43 participants and performed medical records review, clinical examinations and orthopedic inquiry forms. In 23 participants, hip and or spinal imaging assessments were completed. Serial radiographs were analyzed when available. A total of 25 orthopedic manifestations were identified. Ten manifestations were seen in the majority of the participants: hypotonia (87%), ligamentous laxity (85%), scoliosis (63%), kyphosis (58%), characteristic hand deformities (85%), ulnar deviation of the wrist (63%), elbow (55%) and shoulder contractures (65%), tight Achilles tendon (73%), and pes planus (53%). Other characteristics of special note were hip dysplasia (45%), foot deformities requiring surgical intervention (38%) and osteopenia/osteoporosis (47%). We also studied the development of the hips and spine. Uni- or bilateral hip dysplasia was congenital in some, while it developed throughout childhood in others. Spinal involvement included scoliosis, kyphosis, lordosis, and curvature reversal (thoracic lordosis and lumbar kyphosis). Based on these findings, we recommend routine referral to an orthopedic surgeon as well as instituting screening protocols for hips and spine for individuals with Costello syndrome.
authors.affiliation: Genetic Counseling Program, Arcadia University, Glenside, PA, USA.
authors.forename: Stacey
authors.initials: S
authors.lastname: Detweiler
authors.forename: Mihir M
authors.initials: MM
authors.lastname: Thacker
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hopkins
authors.forename: Laura
authors.initials: L
authors.lastname: Conway
authors.forename: Karen W
authors.initials: KW
authors.lastname: Gripp
mesh_terms: D000293:Adolescent; D000328:Adult; D001848:Bone Diseases, Developmental / Q000175:diagnosis / Q000209:etiology* / Q000601:surgery; D002648:Child; D002675:Child, Preschool; D056685:Costello Syndrome / Q000150:complications*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009139:Musculoskeletal Abnormalities / Q000175:diagnosis / Q000209:etiology* / Q000601:surgery; D009985:Orthopedics; D011379:Prognosis; D055815:Young Adult
keywords: Costello syndrome; HRAS; hip dysplasia; orthopedic manifestations